title: Sequenced response of extracellular matrix deadhesion and fibrotic regulators after muscle damage is involved in protection against future injury in human skeletal muscle.
abstract: The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-β1 and collagen types I and III were elevated ∼6- to 9-fold (P<0.001). The findings indicate that the sequenced events of load-induced early deadhesion and later strengthening of skeletal muscle ECM play a role in protecting human muscle against future injury.
authors.affiliation: Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. abigail.mackey@gmail.com
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Mackey
authors.forename: Simon
authors.initials: S
authors.lastname: Brandstetter
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Jens
authors.initials: J
authors.lastname: Bojsen-Moller
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.forename: Mette M
authors.initials: MM
authors.lastname: Pedersen
authors.forename: Simon
authors.initials: S
authors.lastname: Doessing
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
authors.forename: S Peter
authors.initials: SP
authors.lastname: Magnusson
authors.forename: Henning
authors.initials: H
authors.lastname: Langberg
mesh_terms: D000328:Adult; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries*; D009135:Muscular Diseases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012038:Regeneration; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D019063:Tenascin